Insulin-Related Liver Pathways and the Therapeutic Effects of Aerobic Training, Green Coffee, and Chlorogenic Acid Supplementation in Prediabetic Mice

Abstract

Background. The liver controls blood glucose levels via regulation of anabolic (glycogen synthesis and gluconeogenesis) and catabolic (glycolysis and glycogenolysis) processes through activation of the PI3K-AKT signalling pathway. The aim of this study was to assess the effect of aerobic training, green coffee, and chlorogenic acid supplementation on glucose metabolism-regulating pathways in prediabetic mice. Methods. C57BL/6 mice were exposed to a high-fat diet and physical activity limitation to induce a state of prediabetes. After 12 weeks, mice were fed a high-fat diet compared to the control mice. The prediabetic mice were further treated with either green coffee, chlorogenic acid, or training or combinations of the same for 10 weeks. At the end of the experimental period, metabolic data (FBG, GTT, HOMA for IR, plasma level of insulinfrom systematic, AST, and ALT assessed into blood), histopathologic, and analysis of gene and protein expressions were obtained for target tissues. Results. Training along with green coffee and chlorogenic acid supplementation improved complications of prediabetes including weight gain and elevated fasting blood glucose and plasma insulin levels. These effects were associated with the changes in mRNA levels of genes important in hepatic glycogen synthesis (GYS2), glucogenesis (PCK and G6PC2), and glycolysis (GK, PK, and PFKL). Conclusion. The training in conjunction with green coffee or chlorogenic acid is effective in the prevention of prediabetes in mice. As these interventions are relatively inexpensive and safe application to individuals with prediabetes appears warranted.

Green Coffee Bean Extract Potentially Ameliorates Liver Injury due to HFD/STZ-Induced Diabetes in Rats

“…Treatment with GCBE at low and high dosages improved OGTT and increased FPI levels by maintaining healthy glucose homeostasis. Tese fndings were consistent with another study's fndings that GCBE improved OGTT by maintaining normal glucose homeostasis and lowered FPG, improved FPI, and HOMA-IR levels and its efects on lowering FPG [38]. Improving insulin sensitivity may be mediated by up-regulating the expression of glucose transporter type 4 (GLUT4), which can ultimately improve insulin activity and enhance the uptake and utilization of glucose in peripheral tissues [37,39,40].…”

Plant-derived chelators and ionophores as potential therapeutics for metabolic diseases

“…137 This work is supported by observations that the improved conditions of HFD mice treated with chlorogenic acid was related to changes in mRNA levels of genes involved in glucose metabolism like GYS2, PCK, GK, and PFKL. 138 The same effects of chlorogenic acid were observed in human patients with NAFLD or T2D and exhibited similar results with improved metabolic readings. 139 Unsurprisingly, phenolic acids are known to interact with transition metal ions through their carboxylic acid and phenol moieties.…”

The effect of green coffee and/or endurance exercise on sperm function in pre‐diabetic mice

“…At 3 months, the pre-diabetic state of each mouse was confirmed by assessment of fasting blood glucose (FBG) concentration, glucose tolerance test (GTT), HOMA-IR, and plasma insulin in control and pre-diabetic groups. As this study was in continuation of our previous study, for more details are present in Abdollahi et al (2022).…”